Whereas human cytomegalovirus (CMV) replicates productively in the human fibroblast cell strain, WI-38, in bovine embryo fibroblasts (BEF) it causes an abortive infection characterized by cytopathic changes in cell morphology and transient viral antigen synthesis, but with no detectable release of infectious progeny, or assembly of viral particles. The causes of abortive infection are not known, but at least 2 different mechanisms can be postulated: (1) the absence of some essential cellular gene(s) or gene product(s), or (2) the presence of inhibitory product. We will study these alternatives using the technique of cell hybridization between permissive (WI-38) and nonpermissive (BEF) parental cells, and a newer procedure for constructing chimeric cells from cytoplasts and karyoplasts produced by enucleating the parental cells with cytochalasin B. A method based on Edelman's technique for derivatizing petri dishes with antibody (in this case species specific anti-cellular antibody) will be developed and used to separate heterokaryons, hybrids and chimeric cells carrying the cell surface antigens of 2 different species, from their parental cell types. The heterokaryons, hybrids and chimeras will be infected with CMV under a variety of conditions, and the course of viral replication followed by investigating complement fixing and fluorescent viral antigen synthesis, viral DNA replication, viral morphogenesis and release of infectious progeny. Hybrid studies, because of the interaction of the two cell genomes, will show whether the nonpermissive state behaves as a dominant or recessive phenomenon. Chimeric systems, where one set of genes interacts with essentially a single cytoplasm, will give information on the nature and timing of nuclear-cytoplasmic interactions during infection.